Link Between Family Size and Stomach Cancer Found

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Being a member of a large family may not be best for your health. A new study found that family size greatly influenced the development of stomach cancer linked to the bacterium Helicobacter pylori, and younger siblings from large families appeared to be especially vulnerable to the most common type of stomach cancer.

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These latest findings are based on the records of more than 7,000 Japanese-American men who were followed over a 28-year period. The researchers found that those men who carried certain strains of the bacterium in their stomachs and came from families of seven or more siblings were more than twice as likely to develop stomach cancer compared to carriers who had one to three brothers and sisters.

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'This is a very carefully controlled study that clearly shows that there are factors in early childhood that affect the risk of developing cancer many decades later," says Martin J. Blaser, M.D., Frederick King Professor and Chair of the Department of Medicine, and Professor of Microbiology, who led the study. "That early childhood events affect the risk of cancers occurring in old age is remarkable, and this may be a model for other cancers.'

Dr. Blaser speculates that younger children in large families acquire the bacterium from their older siblings at a time when their immune systems are still developing. Since the bacterium has already adapted itself to a genetically related person, namely the older sibling, it has a 'head start' in the younger child, whose immune system is less well defended. This sets the stage for a more virulent, better adapted bacterial population than would occur otherwise if the bacterium was transmitted from a genetically unrelated individual.

H. pylori, a spiral-shaped bacterium that lives in the mucous layer lining the stomach where it can persist for decades, is associated with stomach cancer and peptic ulcers. It is transmitted orally from person to person, such as by sharing saliva, and through contact with human feces. It has been estimated that half the people in the world carry the bacterium in their stomach.

Dr. Blaser is well known for his work with H. pylori. He and his longtime collaborator Guillermo Perez-Perez, DSc., Associate Professor of Medicine and Microbiology, who is also an author on the current study, have explored the bacterium's link to stomach cancer, elucidated genes associated with its virulence, particularly a gene called cagA, and provided evidence showing that the bacterium is mainly transmitted in families.

The current study involves a group of Japanese-American men who lived in Hawaii. These men were first evaluated in the 1960s as part of a heart disease study led by Dr. Abraham Nomura, who also is an author on the current study. The investigators had banked blood samples from 7,429 men who were examined between 1967 and 1975. In the following years, 261 of these men developed cancer.

The current study extends the follow-up of this group to 28 years, providing more reliable data to assess if family structure influenced the risk of cancer. Dr. Blaser and his colleagues, who published a study in the mid 1990s in The New England Journal of Medicine on the relationship between H. pylori and stomach cancer based on this Hawaii cohort, went back to the blood samples from the men who developed stomach cancer and tested the samples for antibodies to H. pylori and the cagA protein. Each of these men were matched with a similarly aged man from the original pool of men who didn't develop cancer.

The researchers assessed whether the risk of stomach cancer was associated with the number of siblings a man had and whether he was older or younger than his brothers and sisters. As in their previous study, they found that men who had cancer were three times more likely to carry H. pylori compared to age-matched men who didn't carry it. Those with cancer had large numbers of siblings.

They also found that in men who had the cagA strain of H. pylori, those from the largest families had the highest risk of stomach cancer. For a type of cancer called intestinal-type gastric cancer, birth order influenced the risk of cancer. In other words, those who had this cancer were likely to be younger siblings.

Dr. Blaser says that it is possible that the findings could be due to factors such as other childhood infections or stress associated with large families. However, based on the genetic studies of H. pylori that he and his colleagues have conducted, he believes that the extraordinary genetic adaptability of H. pylori explains how this bacterium can 'pre-adapt' to a genetically related individual, setting the stage for the development of cancer 50 to 70 years later.

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